The overall goal of this K24 award proposal is to further the development of Dr. Spivack into an exceptional trans-disciplinary patient-oriented research mentor, capable of guiding trainees from developing a clinical hypothesis to formulation of a series of answerable component questions. Key components of that mentorship role will include the articulation of critical aspects of relevant human study design; invoking, where applicable, the creative procurement and analyses of relevant tissue biomarkers by collaboration with appropriate laboratory support; and engagement of sophisticated data analytic techniques to definitively address the hypotheses in a clinically-meaningful manner. The overall aim of the proposal is therefore to support this translational mentorship function. The Specific Aims are: 1) Provide protected time for the PI to further train in epidemiology and statistics, particularly with respect to accrual and analysis of multi-dimensional observational datasets, both case-control/cross-sectional, and prospective cohorts with a time dimension. This will include those studies invoking genetic data analyses, and in prevention trials design and analyses. 2) Provide clinical-translational mentorship for one to two junior clinical faculty members, and a continuous rotation of two to four Pulmonary Medicine or Medical Oncology post-doctoral clinical fellows, at any given time over the project period. 3) Initiate the assessment of prospective cohort-based clinical risk, invoking clinical and airway-specific molecular biomarker analyses of common lung diseases (lung cancer, asthma, COPD), for facilitating the development of early detection and prevention strategies. The current capacity of the Spivack laboratory to develop, sample, accrue and analyze a population, and to conceive, develop and apply state-of-art molecular methodologies for airway disease biomarker analyses to the same population, provides a very unique training opportunity for clinical and other post-doctoral trainees in Medicine, Pulmonary Medicine, Oncology, and in translational research in general. Facilitated by a K24 award, the mentoring experience will be markedly enhanced, as will a shift to evaluating existing prospective cohorts, in a trans-disciplinary manner. The research questions are fundamentally clinical: (1) Can we identify individuals at risk for lung cancer, asthma, and COPD, to facilitate early detection strategies? (2) Can we intervene in individuals, to reduce that risk, using preventive strategies?